Koester, A. M., Geiser, A., Bowman, P. R.T., van de Linde, S., Gadegaard, N. , Bryant, N. J. and Gould, G. W. (2022) GLUT4 translocation and dispersal operate in multiple cell types and are negatively correlated with cell size in adipocytes. Scientific Reports, 12, 20535. (doi: 10.1038/s41598-022-24736-y) (PMID:36446811) (PMCID:PMC9708847)
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Abstract
The regulated translocation of the glucose transporter, GLUT4, to the surface of adipocytes and muscle is a key action of insulin. This is underpinned by the delivery and fusion of GLUT4-containing vesicles with the plasma membrane. Recent studies have revealed that a further action of insulin is to mediate the dispersal of GLUT4 molecules away from the site of GLUT4 vesicle fusion with the plasma membrane. Although shown in adipocytes, whether insulin-stimulated dispersal occurs in other cells and/or is exhibited by other proteins remains a matter of debate. Here we show that insulin stimulates GLUT4 dispersal in the plasma membrane of adipocytes, induced pluripotent stem cell-derived cardiomyocytes and HeLa cells, suggesting that this phenomenon is specific to GLUT4 expressed in all cell types. By contrast, insulin-stimulated dispersal of TfR was not observed in HeLa cells, suggesting that the mechanism may be unique to GLUT4. Consistent with dispersal being an important physiological mechanism, we observed that insulin-stimulated GLUT4 dispersal is reduced under conditions of insulin resistance. Adipocytes of different sizes have been shown to exhibit distinct metabolic properties: larger adipocytes exhibit reduced insulin-stimulated glucose transport compared to smaller cells. Here we show that both GLUT4 delivery to the plasma membrane and GLUT4 dispersal are reduced in larger adipocytes, supporting the hypothesis that larger adipocytes are refractory to insulin challenge compared to their smaller counterparts, even within a supposedly homogeneous population of cells.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Gould, Professor Gwyn and Bryant, Dr Nia and Koester, Anna and BOWMAN, Peter and Gadegaard, Professor Nikolaj |
| Authors: | Koester, A. M., Geiser, A., Bowman, P. R.T., van de Linde, S., Gadegaard, N., Bryant, N. J., and Gould, G. W. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Molecular Biosciences College of Science and Engineering > School of Engineering > Biomedical Engineering |
| Journal Name: | Scientific Reports |
| Publisher: | Nature Research |
| ISSN: | 2045-2322 |
| ISSN (Online): | 2045-2322 |
| Copyright Holders: | Copyright © 2022 The Authors |
| First Published: | First published in Scientific Reports 12: 20535 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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